5-α-Reductase type 2 deficiency: is there a genotype-phenotype correlation? A review.

5-α-Reductase type 2 enzyme catalyzes the conversion of testosterone into dihydrotestosterone, a potent androgen responsible for male sexual development during the fetal period and later during puberty. Its deficiency causes an autosomal recessive disorder of sex development characterized by a wide range of under-virilization of external genitalia in patients with a 46,XY karyotype. Mutations in the SRD5A2 gene cause 5-α-Reductase deficiency; although it is an infrequent disorder, it has been reported worldwide, with mutational heterogeneity. Furthermore, it has been proposed that there is no genotype-phenotype correlation, even in patients carrying the same mutation. The aim of this review was to perform an extensive search in various databases and to select those articles with a comprehensive genotype and phenotype description of the patients, classifying their phenotypes using the external masculinization score (EMS). Thus, it was possible to objectively compare the eventual genotype-phenotype correlation between them. The analysis showed that for most of the studied mutations no correlation can be established, although the specific location of the mutation in the protein has an effect on the severity of the phenotype. Nevertheless, even in patients carrying the same homozygous mutation, a variable phenotype was observed, suggesting that additional genetic factors might be influencing it. Due to the clinical variability of the disorder, an accurate diagnosis and adequate medical management might be difficult to carry out, as is highlighted in the review.

Partial androgen insensitivity syndrome due to somatic mosaicism of the androgen receptor.

BACKGROUND: Androgen insensitivity syndrome (AIS) is the most frequent etiology of 46,XY disorders of sex development (DSDs), and it is an X-linked disorder caused by mutations in the androgen receptor (AR) gene. AIS patients present a broad phenotypic spectrum and individuals with a partial phenotype present with different degrees of undervirilized external genitalia. There are more than 500 different AR gene allelic variants reported to be linked to AIS, but the presence of somatic mosaicisms has been rarely identified. In the presence of a wild-type AR gene, a significant degree of spontaneous virilization at puberty can be observed, and it could influence the gender assignment, genetic counseling and the clinical and psychological management of these patients and the psychosexual outcomes of these patients are not known. CASE PRESENTATION: In this study, we report two patients with AR allelic variants in heterozygous (c.382G>T and c.1769-1G>C) causing a partial AIS (PAIS) phenotype. The first patient was raised as female and she had undergone a gonadectomy at puberty. In both patients there was congruency between gender of rearing and gender identity and gender role. CONCLUSIONS: Somatic mosaicism is rare in AIS and nonsense AR variant allelic can cause partial AIS phenotype in this situation. Despite the risk of virilization and prenatal androgen exposure, the gender identity and gender role was concordant with sex of rearing in both cases. A better testosterone response can be expected in male individuals and this should be considered in the clinical management.

Laparoscopic approach for gonadectomy in pediatric patients with intersex disorders.

The birth of a child with a disorder of sex development (DSD) prompts a long-term management strategy that involves a myriad of professionals working with the family. There has been progress in diagnosis, surgical techniques and in understanding psychosocial issues related to this condition. However, since these kinds of disorders are rare and have many anatomical variations, individual care is necessary, especially regarding surgical management. Gonadectomy is indicated in a number of intersex disorders with a Y chromosome to reduce the associated risk of cancer. Recently, laparoscopy has gained wide acceptance in pediatric urology. Laparoscopy is also reported to be a useful tool for diagnosing and treating DSD because of its minimal invasiveness and favorable cosmetic outcome. However, reports of evaluation and management using laparoscopy for large numbers of DSD patients are limited and debate is still open about indications and timing of gonadectomy. In this study, we reviewed the literature of the last 10 years about the role of laparoscopic gonadectomy in patients with DSD. In the analyzed papers, all the procedures were accomplished successfully using laparoscopy. No conversions to open surgery neither intra-operative complications were reported in all series. Post-operative complications were reported only in one series and included 1 umbilical port infection [2% (1/50)] and 1 pelvic abscess [2% (1/50)], both treated with antibiotic therapy (grade I Clavien-Dindo). Of the analyzed series, 7/10 reported postoperative diagnosis of gonadal tumors. The histopathologic examinations revealed 15 cases of gonadoblastoma, 7 cases of dysgerminoma and 2 cases of seminoma. Analyzing the single series, the incidence of these tumors varied between 10% and 33%. The results of our review confirmed the safety and efficacy of laparoscopic gonadectomy in DSD patients. In our mind, laparoscopic gonadectomy should be accepted as the treatment of choice in children and adolescents with these rare conditions. It thereby eliminates the risk of malignancies of gonadal origin with the advantages of a minimally invasive procedure, with lower morbidity, quicker postoperative recovery and excellent cosmetic results.

Anomalias da diferenciação sexual: representações parentais sobre a constituição da identidade de gênero / Disorders of sex development: parental representations of gender identity construction

O estudo investigou as representações de mães e pais sobre a constituição de identidade de gênero em crianças nascidas com diagnóstico de Anomalias da Diferenciação Sexual (ADS). As ADS são distúrbios da diferenciação sexual que resultam em ambiguidade genital na criança. O estudo tem um delineamento qualitativo, com três mães e três pais de crianças nascidas com ADS, de diferentes idades. Utilizou-se a entrevista narrativa e a análise de conteúdo para coleta e análise dos dados. Os resultados mostraram que mães e pais entendem que a identidade de gênero se constitui através da anatomia da genitália, do sexo de criação com o qual a criança é educada e do reconhecimento social que a criança recebe no ambiente em que vive.(AU)

The present study investigated the representations of gender identity construction by mothers and fathers whose children were born with Disorders of Sex Development (DSD). DSD are disorders of sex differentiation which result in ambiguous genitalia in children. A qualitative study with three mothers and three fathers, whose children of different ages were born with DSD, was carried out. Narrative interviews and content analyses were, respectively, the methodological procedures used to collect and analyze the data. Results showed that the criteria mothers and fathers consider as fundamental for the gender identity construction are the genital anatomy, how the child is raised, and the social recognition of the environment where the child lives.(AU)

Anomalias da diferenciação sexual: representações parentais sobre a constituição da identidade de gênero / Disorders of sex development: parental representations of gender identity construction

O estudo investigou as representações de mães e pais sobre a constituição de identidade de gênero em crianças nascidas com diagnóstico de Anomalias da Diferenciação Sexual (ADS). As ADS são distúrbios da diferenciação sexual que resultam em ambiguidade genital na criança. O estudo tem um delineamento qualitativo, com três mães e três pais de crianças nascidas com ADS, de diferentes idades. Utilizou-se a entrevista narrativa e a análise de conteúdo para coleta e análise dos dados. Os resultados mostraram que mães e pais entendem que a identidade de gênero se constitui através da anatomia da genitália, do sexo de criação com o qual a criança é educada e do reconhecimento social que a criança recebe no ambiente em que vive...

The present study investigated the representations of gender identity construction by mothers and fathers whose children were born with Disorders of Sex Development (DSD). DSD are disorders of sex differentiation which result in ambiguous genitalia in children. A qualitative study with three mothers and three fathers, whose children of different ages were born with DSD, was carried out. Narrative interviews and content analyses were, respectively, the methodological procedures used to collect and analyze the data. Results showed that the criteria mothers and fathers consider as fundamental for the gender identity construction are the genital anatomy, how the child is raised, and the social recognition of the environment where the child lives...